*4.1. Probiotics*

Historically, the theory of probiotics was described by Elie Metchnikoff in 1908, who observed that fermented foods—principally those fermented by lactic acid bacteria—had favorable effects on human wellbeing and longevity. According to the most updated definition based on the Food and Agriculture Organization as well as the World Health Organization, probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [55]. Probiotics related to IBS pathogenesis are mainly those containing *Lactobacillus* and *Bifidobacterium* species [56]. Tentatively, probiotics may promote a favorable modulation of altered gu<sup>t</sup> microbiota

by several mechanisms: reducing the number of competing pathogens by both the production of antimicrobial substances and interfering in intestinal mucosal adhesion [57,58], modulating the metabolism of biliary salts [59], reducing low-grade inflammation [60], and regulating immune activation as well as gu<sup>t</sup> motility [61]. Several meta-analyses of randomized controlled trials (RCTs) that assessed the e ffects of single probiotic strains, compared to a placebo in relieving IBS related symptoms [35,59,62], have concluded that probiotics are more e fficient when compared to placebos in relieving global IBS symptoms including bloating abdominal pain. In safety terms, all studies have reported comparable rates of adverse events to the placebo arms. In an Iranian IBS cohort, Jafari and colleagues observed the e ffects of combinations of strains of *Bifidobacterium*, *Lactobacillus*, and *Streptococcus* genera [63]. The main finding was that 85% of patients in the probiotic group reported satisfactory relief of general symptoms compared with 47% in the control group (*p* < 0.01). In general terms, probiotics seem to have favorable e ffects on improving IBS symptoms, with an excellent safety profile. Nonetheless, more randomized controlled trials are warranted to better define some concerns such as treatment duration and optimal strain, and to better study personalized treatment.
